Press Releases for 2008

NIAMS Scientists Find Potential New Way to Block Inflammation in Autoimmune Disease

Researchers from the National Institute of Arthritis and Musculoskeletal
and Skin Diseases (NIAMS), a part of the National Institutes of
Health (NIH), have identified a promising new target for autoimmune
disease treatment — a cell-surface receptor called DR3. Their research
in mice, published on line in the journal Immunity, suggests
that blocking this receptor could slow or stop the damaging inflammation
characteristic of autoimmune diseases, potentially without leaving
the body vulnerable to serious infections, as many current therapies
do.

DR3 is a protein on the surface of cells. It is a member of the
tumor necrosis factor (TNF) family of receptors, which bind to
molecules related to TNF, a cell-signaling protein that promotes
inflammation. Many of today's most potent treatments for inflammatory
diseases, such as rheumatoid arthritis and psoriasis, interfere
with the action of TNF, thereby blocking inflammation. Since current
anti-TNF therapies don't work in all autoimmune diseases, however,
the researchers turned to the study of DR3, which is a close relative
of TNFR1, the main receptor for TNF.

Working with mouse models of asthma and multiple sclerosis, both
immune system diseases, the researchers found that mice engineered
to lack DR3 were resistant to those diseases. "The implication
is that blocking DR3 in mice, and possibly in humans, is a potential
therapy for these diseases and perhaps others in which the immune
system goes awry," said Richard Siegel, M.D., Ph.D., a scientist
in the NIAMS' Immunoregulation Group, who led the research effort.

While closely related to TNFR1, DR3 is expressed in T cells, a
different kind of immune cell (a white blood cell that identifies
and fights infection) than those that express TNFR1, Dr. Siegel
said. The NIAMS group collaborated with a laboratory in Cardiff,
Wales, which had generated genetically engineered mice deficient
in DR3, as well as with a research group at the NIH's National
Institute of Allergy and Infectious Diseases (NIAID), which has
developed mouse models of disease with strong T cell components,
such as asthma and multiple sclerosis. "These findings open up
new avenues for therapy of these two diseases as well as to other
autoimmune diseases in which T cells play a role in causing or
perpetuating the disease," said Siegel.

The researchers hope that DR3-blocking agents will be effective
anti-inflammatory treatments someday. Siegel noted that if they
were to be used in rheumatic diseases, they would be a complement
to strategies that block TNF because they hit a different arm of
the immune system. "It could be potentially synergistic or complementary," he
said.

Of critical importance, the NIAMS scientists found that removing
DR3 did not appear to suppress the immune response or the ability
to fight infection within the mice — a problem with many other
treatments for autoimmune disease. "We could see the effect of
DR3 deficiency in the diseased organ, but when we looked systemically
at the immune response at other places in the mouse, it was barely
affected," said Dr. Siegel. The group's findings suggest that DR3-blocking
agents might be more effective at specifically treating autoimmune
disease without breaking down the body's defenses against infections,
a long-sought goal of researchers in the field.

NIAID is a component of the National Institutes of Health. NIAID
supports basic and applied research to prevent, diagnose and treat
infectious diseases such as HIV/AIDS and other sexually transmitted
infections, influenza, tuberculosis, malaria and illness from potential
agents of bioterrorism. NIAID also supports research on basic immunology,
transplantation and immune-related disorders, including autoimmune
diseases, asthma and allergies. News releases, fact sheets and
other NIAID-related materials are available on the NIAID Web site
at http://www.niaid.nih.gov.

The mission of the National Institute of Arthritis and Musculoskeletal
and Skin Diseases (NIAMS), a part of the Department of Health and
Human Services' National Institutes of Health (NIH), is to support
research into the causes, treatment, and prevention of arthritis
and musculoskeletal and skin diseases; the training of basic and
clinical scientists to carry out this research; and the dissemination
of information on research progress in these diseases. For more
information about NIAMS, call the information clearinghouse at
301-495-4484 or 877-22-NIAMS (free call) or visit the NIAMS Web
site at http://www.niams.nih.gov.

The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.